ArticleGut2015
Reduced lipoapoptosis, hedgehog pathway activation and fibrosis in caspase-2 deficient mice with non-alcoholic steatohepatitis.
Article in Gut, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.
- Therapeutic potential of mesenchymal stem cell-derived extracellular vesicle in nonalcoholic fatty liver disease: a systematic review and meta-analysis of preclinical evidence.Lipids in health and disease · 2025Pooled it
- Emricasan (IDN-6556) Lowers Portal Pressure in Patients With Compensated Cirrhosis and Severe Portal Hypertension.Hepatology (Baltimore, Md.) · 2019Trial
- Caspase-2 deficiency drives pathogenic liver polyploidy and increases age-associated hepatocellular carcinoma in mice.Science advances · 2026Article
- Three decades of caspases and RIPKs in life and death.Human molecular genetics · 2025Review
- Chronic Nanoplastic Exposure Promotes the Development and Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Casein kinase 1 epsilon (CK1ε) as a potential therapeutic target in chronic liver disease.Journal of veterinary science · 2025Review
- Cigarette Smoke Contributes to the Progression of MASLD: From the Molecular Mechanisms to Therapy.Cells · 2025Review
- Free Cholesterol-Induced Liver Injury in Non-Alcoholic Fatty Liver Disease: Mechanisms and a Therapeutic Intervention Using Dihydrotanshinone I.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Ally or traitor: the dual role of p62 in caspase-2 regulation.Cell death & disease · 2024Article
- Exploring caspase functions in mouse models.Apoptosis : an international journal on programmed cell death · 2024Review
- Chemoproteomics Identifies State-Dependent and Proteoform-Selective Caspase-2 Inhibitors.Journal of the American Chemical Society · 2024Article
- Cell Death in Liver Disease and Liver Surgery.Biomedicines · 2024Review
- Sonic hedgehog-heat shock protein 90β axis promotes the development of nonalcoholic steatohepatitis in mice.Nature communications · 2024Article
- Palmitate induces integrated stress response and lipoapoptosis in trophoblasts.Cell death & disease · 2024Article
- Exosome prospects in the diagnosis and treatment of non-alcoholic fatty liver disease.Frontiers in medicine · 2024Review
- Protective Effect of Vitamin D against Hepatic Molecular Apoptosis Caused by a High-Fat Diet in Rats.Current issues in molecular biology · 2023Article
- Fatty Liver Disease-Alcoholic and Non-Alcoholic: Similar but Different.International journal of molecular sciences · 2022Review
- Role of the Hippo pathway in liver regeneration and repair: recent advances.Inflammation and regeneration · 2022Review
- Genuine selective caspase-2 inhibition with new irreversible small peptidomimetics.Cell death & disease · 2022Article
- Unveiling caspase-2 regulation by non-coding RNAs.Cell death & disease · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
objectiveCaspase-2 is an initiator caspase involved in multiple apoptotic pathways, particularly in response to specific intracellular stressors (eg, DNA damage, ER stress). We recently reported that caspase-2 was pivotal for the induction of cell death triggered by excessive intracellular accumulation of long-chain fatty acids, a response known as lipoapoptosis. The liver is particularly susceptible to lipid-induced damage, explaining the pandemic status of non-alcoholic fatty liver disease (NAFLD). Progression from NAFLD to non-alcoholic steatohepatitis (NASH) results, in part, from hepatocyte apoptosis and consequential paracrine-mediated fibrogenesis. We evaluated the hypothesis that caspase-2 promotes NASH-related cirrhosis.
designCaspase-2 was localised in liver biopsies from patients with NASH. Its expression was evaluated in different mouse models of NASH, and outcomes of diet-induced NASH were compared in wild-type (WT) and caspase-2-deficient mice. Lipotoxicity was modelled in vitro using hepatocytes derived from WT and caspase-2-deficient mice.
resultsWe showed that caspase-2 is integral to the pathogenesis of NASH-related cirrhosis. Caspase-2 is localised in injured hepatocytes and its expression was markedly upregulated in patients and animal models of NASH. During lipotoxic stress, caspase-2 deficiency reduced apoptosis, inhibited induction of profibrogenic hedgehog target genes in mice and blocked production of hedgehog ligands in cultured hepatocytes.
conclusionsThese data point to a critical role for caspase-2 in lipid-induced hepatocyte apoptosis in vivo for the production of apoptosis-associated fibrogenic factors and in the progression of lipid-induced liver fibrosis. This raises the intriguing possibility that caspase-2 may be a promising therapeutic target to prevent progression to NASH.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.